Long-term potentiation (LTP) is a persistent enhancement in synaptic efficacy first discovered in the mammalian hippocampus, which can be induced by brief, tetanic stimulation of afferents to its principal neurons (granule cells of the dentate gyrus and pyramidal cells of the CAI and CA3 regions). I have recently demonstrated that the induction of LTP in the CA3 region of the in vitro hippocampal slice preparation results in the efficacy of heterosynaptic (nontetanized) inputs. Specifically, synaptic responses were recorded from CA3 neurons in pharmacologically disinhibited hippocampal slices using current- and voltage-clamp techniuqes. LTP was induced in one of three synaptic inputs converging onto the same CA3 pyramidal cell: the mossy fibers, the Schaffer collateral/co=issural fibers, and the fimbria to characterize changes in efficacy produced in the other two nontetanized inputs. The results indicate that induction of LTP in the mossy fiber input was accompanied by potentiation of Schaffer and fimbria responses, whereas induction of LTP in the Schaffer pathway was associated exclusively with potentiation of fimbria responses. LTP induced in the fimbria was input specific. Neither the intracellular injection of EGTA into CA3 pyramidal cells, or bathapplication of APV blocks the induction of homosynaptic mossy-fiber LTP and the cojoint heterosynaptic LTP expressed in the Schaffer and fimbrial input. In contrast, the induction of homosynaptic LTP in the same fimbrial input is APV sensitive. The present proposal has four interrelated objectives. i) to determine the causal relationship between homo- and heterosynaptic LTP; ii) to investigate some postsynaptic sequelae which could be responsible for the expression of the maintenance of heterosynaptic LTP; iii) to assess whether NE can enable heterosynaptic LTP; and iv) to determine the relationship between heterosynaptic and associative LTP.